Abstract
Objective
The microbiome contributes to the pathogenesis of inflammatory bowel disease
(IBD) but the relative contribution of different lifestyle and environmental factors
to the compositional variability of the gut microbiota is unclear.
Design
Here, we rank the size effect of disease activity, medications, diet and
geographic location of the faecal microbiota composition (16S rRNA gene sequencing) in
patients with Crohn’s disease (CD; n=303), ulcerative colitis (UC; n = 228) and
controls (n=161), followed longitudinally (at three time points with 16 weeks
intervals).
Results
Reduced microbiota diversity but increased variability was confirmed in CD and
UC compared with controls. Significant compositional differences between diseases,
particularly CD, and controls were evident. Longitudinal analyses revealed reduced
temporal microbiota stability in IBD, particularly in patients with changes in disease
activity. Machine learning separated disease from controls, and active from inactive
disease, when consecutive time points were modelled. Geographic location accounted for
most of the microbiota variance, second to the presence or absence of CD, followed by
history of surgical resection, alcohol consumption and UC diagnosis, medications and
diet with most (90.3%) of the compositional variance stochastic or
unexplained.
Conclusion
The popular concept of precision medicine and rational design of any therapeutic
manipulation of the microbiota will have to contend not only with the heterogeneity of
the host response, but also with widely differing lifestyles and with much variance
still unaccounted for.
Funder
Science Foundation
Ireland
European Crohn’s and
Colitis Organization
Cited by
156 articles.
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